Monday, 30 April 2012

Following some comments posted. Just to let you it is not a question of taking the blog down at present. It is a question of controlling the comments so that they do not put people off visiting.

So you get a flavour, here are some posts arriving in the last day or so..no doubt more to follow. Hope this informs about the trolling and helps inform the voting on the survey.

"b*llsh*tt*r professor get more beer alcohol first remember u need help your mad everyone knows Get help no one likes any of you no ones all b*llsh*tt*rs who have drink probs get more councilling babies"

"Author go f**k yourself full of c**p no drug works pharmas make money like u do all full of po*s*n like u are full of it your attitude is who cares"

"more BS. You are so h*ted. Why because you are mur****ers and all being monitored without knowing. Rumbled all out of jobs soon many ha*e you"

"None of you want to help its all c**p you write and none of you can cope with MS at all. Lawsuits will happen and jobs go hopefully Money making liars"

BACKGROUND AND PURPOSE: Multiple sclerosis (MS) plaques appear as well-demarcated, homogenous small ovoid lesions on magnetic resonance imaging (MRI). Atypical radiographic features of MS lesions include size greater than 2 cm, mass effect (pushing the brain out of the way), and oedema (Swellling). Tumefactive MS lesions can radiographically mimic intra-cranial neoplasms (tumours), infarction (stroke), as well as infections. In atypical cases of tumefactive demyelinating lesions, brain biopsy may be required for the diagnosis.

METHODS: The authors describe the case of a 43 year old woman who presented with worsening right-gaze preference and left side weakness and was initially diagnosed with acute ischaemic stroke. The patient underwent laboratory investigation and brain contrast-enhanced MRI before undergoing brain biopsy.

RESULTS:Fluid attenuation inversion recovery (FLAIR) MRI showed an increase in signal intensity in the right frontal lobe sub-cortical region. Diffusion-weighted imaging showed an area of restricted diffusion involving the white matter of the right-frontal lobe. Cerebrospinal fluid studies were normal except for the presence of oligo-clonal bands. Magnetic resonance spectroscopy (MRS) demonstrated an elevated choline (Cho)/creatine ratio, increase lactate, and normal N-acetylaspartate (NAA)/creatine ratio, findings suggestive of an inflammatory or a demyelinating disease. A brain biopsy of the right frontal lesion was performed and revealed well-demarcated foci of demyelination with axonal preservation. Peri-vascular and parenchymal CD3(+) T-cells were also identified within the demyelinated foci, findings that further supported the diagnosis of active multiple sclerosis.

CONCLUSION:Tumefactive MS can be radiographically misdiagnosed as one of several conditions, among which are infarction, infections, and tumors. Brain biopsy may be needed for diagnosing challenging cases of tumefactive MS.

Prof G has discussed these type of malignant cases of MS in the past, but the importance of this is that in order to diagnose a tumour, which turned out to be MS, they performed a brain biopsy. These have added to the complexity of multiple sclerosis and has suggested that lesions in MS may not be all the same and may harbour some characteristics that are different from lesions that are most typically found in post-mortem tissues, that are often at the end of progressive disease. We will now talk about these lesions

We have been talking about pathology of MS recently. There has been much made of the types of lesions reported by John Prineas of a post-mortem taken after the unusual case of a lethal relapse that showed oligodendrocyte damage in the absence of white blood cells, This has been used my some to question the autoimmune element of MS.

However, as we have also seen that you do not need to have white blood cells around if the damage is triggered by antibodies that can stimulate the microglia to do their worse.

Myelin Stain Myelin Stain Myelin Stain Macrophage (LFB) MOG MAG stain (CD68) * = loss of MAG compared to LFB and MOG. Is this astericks not remyelination, which it looks like it to me?

Patterns 1 and 2 may suggest that myelin/oligodendrocyte is the target, while patterns 3 and
4 suggest the oligodendrocyte may be the target. In pattern 1,
macrophages likely mediate demyelination, whereas in pattern 2, antibody
and complement may contribute to demyelination and is more similar to the autoimmune models, whilst patterns 3 and 4 resemble viral, toxic, ischaemic models. However these latter two lesions are not common in people with SPMS, where the lesions are typically pattern 1 and pattern 2, Pattern III was detected in people with relapsing MS, but this stage responds to immunosuppression, so how do you reconcile this?. However, many pathologists do not agree with these classifications.

As this is MS awareness week, I think we have to
be aware of what you look at and know that you don’t have to believe everything you read.

Who would just orate about nonsense in order to confuse and shape minds? Well it is all over the place. I know “Don’t
believe everything you read” is going to haunt me....as we will get a flurry of comments that "you
talk rubbish blah, blah blah" or thoughts of this at least :-).

However, it is meant to be words of caution. Much of the stuff that we post here will turn out to be wrong, some of it we can spot or suspect when it is published some of it we can not. Maybe we should rate them with numbers of mushrooms to represent the level of "mushroom food" that they represent, but that would get us into trouble with the authors of the papers. However, speaking of mushrooms

Whilst surfing the internet for stuff on CCSVI and reaction to the AAN, I came across a post from someone, a critic of Team G who claims to talk like a Doctor, posting on animal models. It was suggested that "The insight should be compulsory reading for all doctors". Without wanting to bore you with the content but pass on some of the insight. I just wanted to mention their "favorite
description of what's wrong with EAE" (An animal model of MS), attributed to be "from Dr. Michael Dake" (I believe an Interventional radiologist = venoplasty doc). It was written that

"There's an animal model, but it's not
really, unfortunately, like most animal models, it's not really a human model. Basically,
you take like a mish of ground up spinal cord and brain from some other species,
you mix it with some oily substance, some TB bacilli, and some bordatella
pertussis, some whooping cough toxin, and inject it into peridium, and
what you get is this whopping inflammatory response, and that's good because
you get the accelerated disease process, but obviously in humans, it's a much
more chronic and progressive thing"....."People
with MS haven't had this cocktail of viruses injected into their brains”

Dr. Dork seemingly has no real knowledge of doing experimental MS
work or maybe there are loads of typos (I know kettle and black :-)) or it was just lost in translation but this is a description of a new model
variant in a MUSHROOM. This would be good 3Rs stuff but..

Let us look at what was written. First off it is an animal model of human disease. A human model "of human disease" would involve experimenting on humans, which I don't think is ethical for drugs just comming off the drawing board, although it has been suggested by someone on the Blog.....really. Yes, people do experiment on MS, but this is not a model, it is the real thing!

I accept that the method to induce MS-like disease sounds unpleasant but lets look at the content of the above insightful? :-) comments.

You take a mixture of ground up spinal cord and brain. [WRONG. You take spinal cord because it contains comparatively more myelin in the rodent and you do not usually use brain, which often would not work] from some other species [WRONG. You usually take from the same species. There are cases such as in rats where guinea pig spinal cord was often used], you mix it with some oily substance [Freunds incomplete adjuvant], some TB bacilli [Misleading. These are killed Mycobacterium tuberculosis-the bacteria that causes tuberculosis and/or Mycobacterium butyricum and is then called Freunds complete adjuvant. This is used to stimulate the immune system to the substance mixed with it], some bordatella pertussis [WRONG It is Bordetella pertussis toxin, which is the toxin from the bacteria causing whooping cough. Killed Bordettela pertussis bacteria are not usually used to induce EAE compared to the toxin that is used. This makes white blood cells divide and grow. This is often not required to induce EAE]. Whooping cough toxin [This is Bordetella pertussis toxin as above....so you are doing the same thing that is already mentioned] and inject it into the peridium [WRONG. This is a covering of where the spores of a fungi are stored. Mushrooms are fungi. Fungi are not animals so it would not be an animal model but a mushroom model :-). Was the word perineum I doubt it, but maybe peritoneum, which is the peritoneal cavity which is the bit where you intestines live below the lungs. However, this is largely WRONG as it is usual to inject under the skin].You get the accelerated disease process, but obviously in humans, it's a much
more chronic and progressive thing [WRONG so what? They would not be much of a model if you had to wait twenty to thirty years for it to develop or last fifty years. Animal models have been developed that develop progressive and chronic disease]. People
with MS haven't had this cocktail of viruses [WRONG there has been no introduction of viruses, the injection protocol above uses killed bacterial products] injected into their brains [WRONGit would not work if injected into the brain, because they have limited lymph gland drainage, it is injected under the skin so the immune-causing material is directed towards the lymph nodes].

P.S. The rest of the commentary centres around neutrophils, which are not reported to have much of a role in MS, and apparent differences between animals and humans.

There is lots of information of the web, some of it is more accurate than other stuff. Do you remember Doing a scully (another post on mushrooms). You need to do your homework and check words to make sure that you understand what is being said and importantly to convince yourself that it is accurate. It is easy to throw in some science that sounds plausible but does not hang together coherently. Check out the source of the fact, is it some company blurb, a reputable source or a crusader. It is easy to pass a lot of information off as fact, when it may be meerly mushroom food.

Sunday, 29 April 2012

To People who get their Posts from Feeds and Miss the Comments. You may be less inclined to visit the main site and vote. However you will have noticed the Trolling Posts. Please Come and Vote as it will influence how the blog operates

To help you consider your voting, here are the details for Aprils (1:4:12-28:4:12) Comments. There may be a few errors as it was not recounted to verify, so there may be small errors.

____________________________________________

POSTED COMMENTS Spammed Recieved

____________________________________________

ANONYMOUS * N/A 92

ID (Identified name) N/A 78

TEAM G N/A 135

___________________________________________

* During April Anonymous posting was stopped two times due to trolling lasting over 7 days

If you remove comments you do not get any hate mail, you (MSers) do not recieve nonsense email alerts but you do not get any questions and answers. The blog then becomes less unique. The more comments the more work for Team G. There were responses from 4 Team G members.

If you remove ANONYMOUS comments you exclude the majority of the comments comming onto the blog. Some people want to hide behind anonymous to post pointed-questions or answers. Some people are not out and this makes it easier for them to comment. It may not be representative of every month but I think the majority of comments always comes from the anonymous and we have turned this feature off twice this month because of trolling, therefore the ratio of anon verse ID comments could be higher.

You can hide with a fake ID, as some people do, even to post perhaps pointed questions, however the comments from the ID came from only 26 differnent ID. This is presumably a very small fraction of the readers. However you take an identify were you are responsible for your comments, people can see who you are.

To answer comments these have to be read, which is moderation after the posting.

______________________________________________

ADVERTISING MAIL Spammed Received

ANON 0 0

ID 0 2

_______________________________________________

This usually comes from ID sources where some company etc posts a comments and then a link to some product. This often comes after a post mentioning a potential product and one wonders to what extent google is responsible for this. Although some have been spammed (often by the google filter). These are often reposted minus the link (to avoid claim of censorship) as they are harmless and some may carry some element of informative comments. Therefore there is Moderation. To remove advertising you have to allow no comments or moderate comments

______________________________________________

Insult Mushroom HATE MAIL Spammed Death/Killing Lawsuit Food

______________________________________________

ANON 48 31 9 17

ID 0 N/A N/A N/A

______________________________________________

It is clear that the overt insults not appropriate for the website come from Anonymous posting, many within minutes of each other all over the blog, as a trolling event.

This month this has been the most yet and have had more spamming events than at any time in the history of the Blog We do not like spamming comments

You will note the 48 threats insults add up to 57 different types that were split into three groups as many contained
double insults. Saying doctors are rubbish was not a spamming criteria, disagreeing with our point of view is not. You could probably merge the lawsuit and mushroom food
items together as they are both mushroom food. You either allow no anonymous comments or you have to moderate them to allow anonymous comments and limit the hate mail.

Moderation of comments takes time and effort. Comments do not appear instantly (could be just once a day) and have to be read by a member of Team G for approriateness (what does that mean? Therefore you could claim censorship and lack of free speech). However, we must eliminate the trolling for the benefit of our more sensible readers that are the majority.

Maybe
when you next start trolling, perhaps you could add abit about ageism,
racism, sexism when you insult us and then we can get Google to hunt
you down.

Background and objectives: It is widely accepted that typical acute demyelinating lesions in relapsing-remitting multiple sclerosis (RRMS) exhibit vasogenic oedema with increased diffusion, as demonstrated by an increased apparent diffusion coefficient on MRI. In contrast, acute ischemic lesions demonstrate cytotoxic oedema with restricted diffusion. Recent reports have documented selected cases of acute demyelinating lesions exhibiting restricted diffusion (ADLRD) in MS. We aimed to assess the morphologies, distributions, signal characteristics and changes over time of nine ADLRD. An additional goal was to obtain clinical correlations and relate our findings to all previously published case reports describing ADLRD.

Methods: A retrospective case series study was performed at two academic centers. MRI characteristics of nine ADLRD found in six RRMS patients were compared with typical active symptomatic contrast-enhancing lesions with increased or normal diffusion in control RRMS patients.

Results: The average size of ADLRD was not significantly different from typical lesions. A periventricular location and faint signal on T2-weighted images were significantly more common for ADLRD compared with typical lesions. Two patients with ADLRD on initial MRI exhibited new ADLRD on their follow up scans.

Conclusion: Our results and review of prior published cases suggest that ADLRD represent a new variant of MS lesion. The restricted diffusion that is a characteristic of ADLRD on MRI is a new challenge in the differential diagnosis of stroke in young adults. The pathogenesis of ADLRD remains to be understood

Fortunantely the people on whom these images were performed as still living and to make real sense of what is going on, one would like to see histology of the ADLRD lesions to know if they are like stroke lesions and hypoxic (lack of oxygen-poor blood flow?) or not. Do they correspond to the Pattern III white matter lesions? (Whats this-find out tomorrow), Does this link with CCSVI? This is the problem of using MRI analysis on MSers to define what is going on, it is all supposition with little real science and this is perhaps why many of the MRI parameters do not have any real pathological correlate.

BACKGROUND: Recent findings support the important role of antibodies in multiple sclerosis (MS) physiopathology. Thus, local IgG synthesis is a hallmark of the disease, and intrathecal IgM synthesis associates with a poor disease outcome.

METHODOLOGY: The aim of this study was to investigate the presence of IgM (contains five IgG like molecules that are weak binder to targets) and IgG (usually strong bindiers to targets) in demyelinating lesions using high sensitivity immunohistochemistry techniques in necropsies from fourteen MS patients, four controls without neurological disease and four cases with non MS CNS inflammatory disease.

RESULTS: IgG and IgM were absent in controls. Conversely, we found IgM in about 50% and IgG in 75% of MS patients. The presence of IgM and IgG antibodies was independent of disease duration, clinical disease type or lesion stage. IgM and IgG were present in acute, chronic active and chronic inactive lesions. Double immunofluorescence showed that IgM and IgG were detected on axons and oligodendrocytes in demyelinated areas. Moreover, we observed immunoglobulin deposits on oligodendrocytes in NAWM in some cases. IgG and IgM colocalized with complement C3b on demyelinated axons and oligodendrocytes and antibody-antigen immunocomplexes were detected in foamy macrophages in active lesion areas. These findings were absent from cases of non-neurological disease and cases with non-MS CNS inflammatory disease.

CONCLUSIONS:These observations provide further evidence on the role of antibodies, complement and macrophages in plaque development, and strongly suggest they can induce axonal injury, an important cause of disability in MS. They may provide novel therapeutic strategies to limit tissue degeneration in the disease.

Complement cascade (yes it is complicated)

Much has been made about the John Prineus studies of oligodendrocyte damage without the presence of lymphocytes (white blood cells). However they don't need to be near the damage if their function is to help B cells to secrete antibodies that can travel widely throughout the central nervous system, once it passed the blood brain barrier or is secreted inside the brain. The presence of antibody (IgG and IgM) and complement (cascade of molecules that end up punching holes via the membrane attack complex in cells to kill them or can provide a signal for macrophages or microglia to engulf (Opinsinization) the target expressing complement).

There is an immunology lession that needs to be given. The fact that it is present in normal appearing white matter, which is seemingly normal tissue, suggests that this could be an early event in lesion formation and that normal appearing white matter may be destined to become the pre-active lesion (see espresso pathology posts)

In a retrospective study, we included 64 children and adolescents who were diagnosed with relapsing–remitting MS and who were referred to MRI including venography (MRV) during the first 4 months of disease onset. For a control group, we collected 54 MRV data of children, who had been investigated with MRI for different clinical reasons (headache, epileptic seizures, vertigo), but who showed neuroradiologically inconspicuous results. The cross-sectional blood vessel areas of the internal jugular veins were measured at the base of the skull and the narrowest part of the vein in its course; the lumen reduction was computed as a ratio, accordingly. Three groups were defined and a ‘relative’ stenosis value (SV) assigned to each group: (1) 0–50% vessel narrowing → SV 0, (2) 51–80% vessel narrowing → SV 1 and (3) >80% vessel narrowing → SV 2. The venous SV score was determined by summation of the SV of both sides. In both groups we saw a high prevalence of venous narrowing displayed by a mean SV score of 2.6 (SD 1.3) in the MS group and 2.9 (SD 1.2) in the control group. Only six paediatric MS patients and three controls did not show any internal jugular vein narrowing. In contrast, 20 MS patients and 20 controls presented with bilateral internal jugular vein narrowing above 80%. Differences between the two cohorts were not statistically significant. No correlation was found with the clinico-neurological parameters of disease. In summary, internal jugular vein narrowing is a frequent finding in children and adolescents independent of the diagnosis of MS.

If CCSVI is central to the causation of MS you would expect the problem to be found in children before multiple sclerosis is diagnosed. This suggests that there is detectable apparent narrowing of veins, but that they also occur in non MSers, which may question the significance of this in the causative role. Of course you may say that this was a retrospective study and that they did not have MS when the assessment of vein function was made so the veins were not blocked until MS developed, but then we had this next post also

Objective: Chronic cerebrospinal venous insufficiency (CCSVI) was hypothesized to play a causative role in multiple sclerosis (MS). The assessment of pediatric-onset MS (POMS) may provide a unique window of opportunity to study hypothesized risk factors in close temporal association with the onset of the disease.

Methods: Internal jugular veins, vertebral veins and intracranial veins were evaluated with extracranial and intracranial ultrasound in 15 POMS and 16 healthy controls. Assessor’s blinding was maintained during the study. We considered subjects positive to CCSVI when at least two criteria were fulfilled.

Results: CCSVI frequency was comparable between POMS and controls (p > 0.05). Clinical features were not significantly different between CCSVI-positive and CCSVI-negative patients.

Conclusions: Our findings add to previous data pointing against a causative role of CCSVI in MS.

Source

Endovascular intervention for obstruction to venous drainage of the head and neck is an established treatment for disorders such as superior vena cava syndrome. Some patients with multiple sclerosis have been observed to have anomalies of the veins draining the head and neck. It is possible that some symptoms associated with multiple sclerosis may be secondary to disturbed venous flow. In an uncontrolled clinical series of 40 patients who had been previously diagnosed with multiple sclerosis, anomalies of the venous drainage of the head and neck were observed, including venous stenoses of the internal jugular veins. In 38 of 40 patients, venous stents were placed with restoration of luminal dimensions and abrogation of the venous pressure gradient. The angiographic and hemodynamic improvement was associated with improvement in symptomatology, most particularly in cognitive and constitutional symptoms that may be related to cerebrovenous flow. Serious complications included death in one subject and stent embolization requiring open heart surgery in another. In conclusion, in this series, endovascular intervention to correct venous stenosis associated with multiple sclerosis was associated with improvement in symptoms possibly related to disturbed venous haemodynamics. However, given the serious adverse events in this small series, a randomized clinical trial is required to confirm these findings, and to determine if the procedure has any effect on the progression of multiple sclerosis, or untoward long-term adverse effects.

This study hailed from Stanford in the USA, which treated the husband of our friend Joan Beal. On face value this sounds promising, with the caveat of the problem. If replicated in randomised trial

Source

BACKGROUND AND PURPOSE:CCSVI hypothesizes an association between impaired extracranial venous drainage and MS. Published sonographic criteria for CCSVI are controversial, and no MR imaging data exist to support the CCSVI hypothesis. Our purpose was to evaluate possible differences in the extracranial venous drainage of MS and healthy controls using both TOF and contrast-enhanced TRICKS MRV.

RESULTS: The 2 groups were matched for age and sex (MS, 45 ± 8 years, 79% female; healthy controls, 47 ± 10 years, 65% female). Reader agreement for IJV flattening and collateral severity was good (κ = 0.74) and moderate (κ = 0.58), respectively. While IJV flattening was seen in both patients with MS and healthy controls, scores for the patients with MS were significantly higher (P = .002). Despite a trend, there was no significant difference in collateral scores between groups (P = .063). Mushroom food this means there was no difference. There was a significant positive correlation between flattening and collateral scores (ρ = 0.32, P = .005) and EDSS and flattening scores (ρ = 0.45, P = .004) but not between EDSS and collateral scores (ρ = 0.01, P = .97).

CONCLUSIONS: These results indicate that patients with MS have greater IJV flattening and a trend toward more non-IJV collaterals than healthy subjects. The role that this finding plays in the pathogenesis or progression of MS, if any, requires further study.

This study hailed also from Stanford in the USA. On face value this suggests vascular effects in MSers, the more apparent flattening is associated with more disability

Background: Magnetic
resonance imaging and echo color Doppler (ECD) scan techniques do not
accurately assess the cerebral venous return. This generated
considerable scientific controversy linked with the diagnosis of a
vascular syndrome known as chronic cerebrospinal venous insufficiency
(CCSVI) characterized by restricted venous outflow from the brain. The
purpose of this study was to assess the cerebral venous return in
relation to the change in position by means of a novel cervical plethysmography method.

Methods: This was a single-center,
cross-sectional, blinded case-control study conducted at the Vascular
Diseases Center, University of Ferrara, Italy. The study involved 40
healthy controls (HCs; 18 women and 22 men) with a mean age of 41.5 ±
14.4 years, and 44 patients with multiple sclerosis (MS; 25 women and 19
men) with a mean age of 41.0 ± 12.1 years. All participants were
previously scanned using ECD sonography, and further subset in HC (CCSVI
negative at ECD) and CCSVI groups. Subjects blindly underwent cervical
plethysmography, tipping them from the upright (90°) to supine position
(0°) in a chair. Once the blood volume stabilized, they were returned to
the upright position, allowing blood to drain from the neck. We
measured venous volume (VV), filling time (FT), filling gradient (FG)
required to achieve 90% of VV, residual volume (RV), emptying time (ET),
emptying gradient (EG) required to achieve 90% of emptying volume (EV)
where EV = VV-RV, also analyzing the considered parameters by receiver
operating characteristic (ROC) curves and principal component
mathematical analysis.

Conclusions Cerebral
venous return characteristics of the patients with CCSVI were markedly
different from those of the controls. In addition, our results suggest
that cervical plethysmography has great potential as an inexpensive
screening device and as a post-operative monitoring tool.

Once validated by others, tools to screen and monitor efficacy (if present) duration will be very useful.

METHOD: One hundred and sixteen IJVs were assessed in 58 patients with associated multiple sclerosis. Findings of Doppler sonography were compared with results of the reference test: catheter venography.

RESULTS: At least one positive extracranial sonographic criterion suggesting venous abnormality was found in 92.2% of the assessed veins. Yet, sensitivity, specificity, positive and negative predictive values of sonography were low: 93.4%, 12.0%, 79.4% and 33.3% for at least one positive criterion, and for at least two positive criteria: 29.3%, 75.0%, 81.8% and 21.7%, respectively.

CONCLUSIONS:Our research has shown that currently used extracranial sonographic criteria for the detection of obstructive venous abnormalities in the IJVs are of limited diagnostic value. For the time being, diagnosis of this vascular pathology should be given using catheter venography.

Whilst this study is finding ultrasonic changes in most MSers, this is not sufficient for CCSVI. This study adds no clarity and it seems clear to me that there needs to be guidelines and adherence to methods of assessment and adherence to criteria for definition of CCSVI that should be required for publication. This is because more and more ill-defined studies helps no one and adds to confusion. I suppose however it questions the technology of sonography for detecting anything.

OBJECTIVES: The traditional view that multiple sclerosis (MS) is an autoimmune disease has recently been challenged by the claim that MS is caused by chronic cerebrospinal venous insufficiency (CCSVI). Although several studies have questioned this vascular theory, the CCSVI controversy is still ongoing. Our aim was to assess the prevalence of CCSVI in Danish MS patients using sonography and compare these findings with MRI measures of venous flow and morphology.

RESULTS: US-CD could not identify the left internal jugular vein (IJV) in one MS patient, other ultrasound examinations were normal in patients with MS. There was no difference in mean cross-sectional area of the IJV in MS patients compared with controls. Only one patient with MS and two healthy controls fulfilled one CCSVI criterion, and none fulfilled more than one CCSVI criterion. MR venography showed insignificant IJV stenosis (1-49%) in two patients with MS, whereas 50-69% IJV stenosis was detected in two healthy controls. There was no difference in PC-MR measurements of mean IJV blood flow between patients with MS and controls.

CONCLUSION: Our results do not corroborate the presence of vascular pathology in RRMS and we found no evidence supporting the CCSVI hypothesis.

You can read the the conclusion and maybe you will argue that it depends on protocol.

OBJECTIVE: To assess for venous abnormalities possibly related to CCSVI in MS and control cadavers.

BACKGROUND:
Chronic cerebrospinal venous insufficiency is a new theory of MS
pathogenesis involving alterations in cerebral venous outflow. There has
been little pathologic study of venous structures related to CCSVI.

RESULTS:
Valvular and other intraluminal abnormalities with potential
hemodynamic consequences were identified in 5 of 7 MS patients (7
abnormalities) and in 1 of 6 controls (1 abnormality). These
abnormalities included circumferential membranous structures (1 MS; 1
control), longitudinally-oriented membranous structures (3 MS), single
valve flap replacing IJV valve (2 MS), and enlarged and malpositioned
valve leaflets (1 MS). Significant stenosis was seen in 2 MS and 1
control. Additionally, several minor anatomic variations without
expected hemodynamic consequences were observed similarly in both MS and
controls. These included valves with 3 leaflets, the presence of AZY
valves, additional (duplicate) normal-appearing IJV valves, and small
accessory valve leaflets. Histologic evaluation is underway and will be
reported along with additional cases. CONCLUSIONS: Post mortem
examination of the IJV and AZY veins in MS and non-MS controls
demonstrated a variety of structural abnormalities as well as anatomic
variations. Vein wall stenosis occurred at similar frequency in both
groups. However, the frequency of intraluminal abnormalities with
possible hemodynamic consequences appeared higher in MS patients
compared to healthy controls, although the current sample size is
limited. These results suggest that MRV studies evaluating vein wall
stenoses may be less effective than ultrasound in identifying venous
abnormalities in CCSVI. In addition, CCSVI ultrasound studies should
include focused evaluation of intraluminal abnormalities

You can read the conclusions, but surely it is important to have performed the ultrasound to check that the criteria of CCSVI was fullfilled before assessing histologically. Without this knowledge there are clear problems, but if there was 100% specificity for MS as originally claimed then that would not be an issue. However I think most other studies are not showing a 100% and so this is important in the validity of the study.

OBJECTIVE: This
systematic review was undertaken to examine the evidence of an
association between chronic cerebrospinal venous insufficiency (CCSVI)
and multiple sclerosis (MS) using rigorous methodological analyses.

BACKGROUND:
It has been proposed that MS is caused by ultrasound detectable
abnormalities in the anatomy and flow of intra and extra-cerebral veins,
a condition termed CCSVI.

DESIGN/METHODS: A literature search of
Ovid MEDLINE, the Cochrane Central Register of Controlled Trials and
EMBASE was conducted. Eligible studies used ultrasound to diagnose CCSVI
and compared MS patients with either healthy controls (HC) and/or
patients with other neurological diseases (OND). A random effects model
was used and odds ratios (OR) and I2 values were generated.

RESULTS:
Eight studies compared the frequency of CCSVI in MS patients vs. HC; 4
studies compared MS vs. OND. CCSVI diagnosis was more common in MS vs.
HC (OR 13.5, p=0.002), but there was marked heterogeneity in both the
frequency and magnitude of this association. A statistically significant
but reduced association remained using the most conservative analysis
(OR 3.4, p=0.02), which involved removing Zamboni's initial study and
adding a negative CCSVI study. The studies comparing MS and OND also
found CCSVI more commonly in MS, but this was not statistically
significant (OR 32.5, p=0.09). The OR dropped to 3.4 (p=0.11) with
removal of Zamboni's study. No study reported tests of blinding of
technicians or radiologists.

CONCLUSIONS: This systematic review
did find a statistically significant greater odds of CCSVI in MS
patients vs. HC, but not in MS vs. OND. Limitations including
uncertainty regarding blinding and marked heterogeneity of the results,
and do not allow for definitive conclusions. These early results raise
the possibility that CCSVI may not be MS-specific, and it may follow,
not precede onset of disease. Further high quality controlled studies
are needed to definitively determine if CCSVI is truly associated with
MS.

OBJECTIVE:
To investigate the association between presence of a newly proposed
vascular condition called chronic cerebrospinal venous insufficiency
(CCSVI) and environmental factors in a large volunteer control group
without a known central nervous system pathology.

BACKGROUND: The
role of intra- and extra-cranial venous system impairment in the
pathogenesis of various vascular, inflammatory and neurodegenerative
neurological disorders, as well as in aging, has not been studied in
detail.

DESIGN/METHODS: The data were collected in a prospective
study from 252 subjects who were screened for medical history as part of
the entry criteria and participated in the case-control study of CCSVI
prevalence in multiple sclerosis (MS) patients and were analyzed post
hoc. All participants underwent physical and Doppler sonography
examinations, and were assessed with a structured environmental
questionnaire. Fullfilment of ≥ 2 positive venous hemodynamic (VH)
criteria on Doppler sonography was considered indicative of CCSVI
diagnosis. Risk and protective factors associated with CCSVI were
analyzed using logistic regression analysis.

RESULTS: Seventy
(27.8%) subjects presented with CCSVI diagnosis and 153 (60.7%)
presented with one or more VH criteria. The presence of heart disease
(p=.001), especially heart murmurs (p=.007), a history of infectious
mononucleosis (p=.002), and irritable bowel syndrome (p=.005) were
associated with more frequent CCSVI diagnosis. Current or previous
smoking (p=.029) showed a trend for association with more frequent CCSVI
diagnosis, while use of dietary supplements (p=.018) showed a trend for
association with less frequent CCSVI diagnosis.

OBJECTIVE: Does
chronic cerebrospinal venous insufficiency (CCSVI) exist, is it
associated with multiple sclerosis (MS), and what tools might establish
its presence? We sought to determine if neurosonography (NS) provides
reliable information on cerebral venous outflow patterns, if NS findings
are supported by 3T magnetic resonance venography (MRV), and if NS
and/or MRV reflect transluminal venography findings. We detail NS
findings on the first 193 participants. BACKGROUND: CCSVI is postulated to have a role in MS pathogenesis. DESIGN/METHODS:
TB, blind to the subject's diagnosis, used high resolution B-mode
imaging with color and spectral flow Doppler to investigate extracranial
and intracranial venous drainage. Results were evaluated by ADB with
neither subject contact nor patient information; only KT and JSW could
access the complete database. RESULTS: 10 healthy controls, 18
cerebrovascular diseases, 27 other neurological diseases, 138 MS (7
clinically isolated syndrome, 80 relapsing remitting, 35 secondary
progressive, 15 primary progressive, 1 progressive relapsing) were
studied. MS patients were older than non-MS subjects (48.4±9.8 v
44.3±11.4 years), durations from first symptoms and diagnosis of
13.7±9.4 and 10.3±8.0 years, and EDSS 2.9±2.0. 47 subjects fulfilled one
of five criteria for CCSVI proposed by Zamboni; 8 fulfilled two
criteria and none fulfilled >2 criteria. The distribution of subjects
with 0, 1 or 2 criteria did not differ significantly across all
diagnostic groupings, between MS and non-MS subjects, or within the MS
subgroups. No significant differences emerged between MS and non-MS
subjects for measures of cross-sectional areas of the internal jugular
veins at fixed anatomic sites or for extracranial or intracranial venous
flow rates. CONCLUSIONS: NS findings described as CCSVI are much
less prevalent than previously reported and do not distinguish MS from
other subjects. Data will be updated prior to the meeting. Correlations
of NS and MRV for 37 MS subjects are reported separately.

This is a pretty damming report against the CCSVI concept being real.... but the protocol was not the Prof Z way I hear you say.

OBJECTIVE:
Does chronic cerebrospinal venous insufficiency (CCSVI) exist, is it
associated with MS, and what tools might establish its presence? Steps
included: determine if neurosonography (NS) provides information on
cerebral venous outflow patterns suitable as a first screen, learn if NS
findings are supported by 3T magnetic resonance venography (MRV) of the
head, neck, chest, abdomen and pelvis, and evaluate if NS and/or MRV
reflect 'true' venous anatomy seen by transluminal venography (TV). This
report details the correlation of MRV and NS findings on the first 37
MS participants to undergo both procedures. BACKGROUND: CCSVI has a postulated role in multiple sclerosis (MS). DESIGN/METHODS:
Participants provided informed consent. Extracranial and intracranial
venous drainage was investigated with high resolution B-mode imaging
with color and spectral flow Doppler, performed and recorded by TB,
blind to the subject's diagnosis. MRV utilized AblavarTM to improve
vascular visualization. NS results were evaluated by ADB, MRV images by
LAK; neither had access to subject information or the other's data. Only
KT and JSW had complete database access. RESULTS: MS clinical
phenotypes included 1 clinically isolated syndrome, 24 relapsing
remitting, 6 secondary progressive, 5 primary progressive and 1
progressive relapsing. Delay from NS to MRV was 160±77 days. NS
identified 14/37 subjects fulfilling 1 of 5 Zamboni criteria for
anomalous venous outflow; only 1/37 fulfilled 2 criteria required for
CCSVI. MRV identified 5/37 subjects with venous stenosis; 1 Type A and 4
Type C patterns. A Zamboni score <2 by NS was concordant with a
normal venous vascular patterns on MRV for 31/36 subjects, but
discordant for the subject with Zamboni score on NS of 2. CONCLUSIONS:
There was reasonable correlation of between independent assessments of
Zamboni scores on NS and patterns on MRV. These studies suggest that
findings described as CCSVI are not common.

Therefore one must ask why treat a condition that evidence is suggesting does not really exist. Anyway lets wait for the trials and see if the treatment is beneficial

OBJECTIVES: Recently an association has been made
between Multiple Sclerosis (MS) and Chronic Cerebrospinal Venous
Insufficiency (CCSVI) characterized by stenosis and reflux of the
principal extracranial venous drainage including the Internal Jugular
veins (IJV) and the Azygous veins (AZV). This is the first angiographic
study to quantitatively analyze the impact of percutaneous balloon
angioplasty (PTA) on flow dynamics across these lesions.

METHODS: 50 IJV from MS patients with CCSVI and 12
IJV from healthy volunteers underwent detailed angiographic evaluation.
Technical components of all venograms were standardized. Quantitative
analysis included the contrast time of flight (TOF) from the mid IJV to
the superior vena cava, and the primary venous emptying time (PVET),
quantified as >50% of venous emptying, from the IJV. The TOF and PVET
were recorded in patients with CCSVI prior and subsequent to balloon
angioplasty, as well in normal healthy subjects. All data was
prospectively collected, and statistical analysis was performed using
two-tailed Student’s test.

RESULTS: Of the 50 CCSVI-MS patients with IJV
stenosis >70% and reflux underwent balloon angioplasty, technical
success defined as <20% residual IJV stenosis was achieved in 78%
(44/50). Table describes the pre- and post-angioplasty TOF and PVET in
patients with CCSVI, as well as in healthy non-MS patients without any
treatment. CCSVI patients were noted to have a significant improvement
in both the TOF and PVET following balloon angioplasty that paralleled
healthy non-MS subjects.

CONCLUSIONS: Results of this prospective pilot study
suggest an association between MS and CCSVI, which results in
abnormally elevated TOF and PEVT through the IJV. Furthermore, balloon
angioplasty these lesions improves the hemodynamic parameters that are
comparable to healthy non-MS patients.

Table

MS patients with CCSVI

Healthy Non-MS

p-Value

Pre-Angioplasty

Post-Angioplasty

No Treatment

TOF

PVET

TOF

PEVT

TOF

PEVT

Mean Time (sec.)

5.28

12.45

2.45

6.44

2.33

6.10

<0.001

St. Dev.

2.52

10.0

0.79

2.05

0.42

0.58

There is still no clarity and some reports may have been missed (based on pubmed) or were too uninteresting/irrelevant to comment on but some interesting publications have been published this month, there may be a weight of evidence building towards the negative side. We must remember that meeting abstracts have not been properly peer-reviewed and we will need to wait until they are published. I think I will concentrate on published obersvations in future also as the subjects in meetings abstracts will occur elsewhere and this gives bias and the information keeps appearing, unless we hear of the results of the blinded trials.

Why do we not take comments on these posts?

Experience-We learn from the past. I know that this would be managable whilst comments are being read first, but it also saves us being accused of selecting what goes public.

We are sure many of you would like to make sensible comments that are valid to the debate, but due to probably a minority who spoil it for the majority, we have no desire to recieve and are saddened by the personal abuse that we sometimes, have to endure, such as the beginning of this month and a few days ago and yesterday and the day before that and that etc. We hope you understand.

We are essentially giving you the information and you can make you own mind up! Should we stop posting on this subject, well no because it is topical and you can see the weight of evidence accumulate, but is is only a very small part of MS research..

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